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P Berthon

Publications and source records attributed to P Berthon.

At least 19 recordsLinked to original sources
PubMed2003

[Collections of human biological resources for research purposes: from regulations to the need of a guide of good collection practices].

PURPOSE: In France, collections of human biological resources are regulated by the "Bioethics Law", currently in revision. Hence, we analyse the regulatory and ethical issues of these practices in the context of scientific research. The ultimate aim of such collections is to improve biological and medical knowledge. CURRENT KNOWLEDGE AND KEY POINTS: We think that the French regulatory system is quite complicated and non-explicit for "collection holders". The multiplicity of legal texts concerning this activity has made their application difficult, especially in the absence of application decrees. The project amending the actual law has clarified the legal status of collections but it did not shed light on the status of human body detached parts. Furthermore, the text is still very far from the international bioethical recommendations, and does not reflect the actual collection's implementation. FUTURE PROSPECTS AND PROJECTS: The establishment of a guideline of Good Collection Practices, based on clear principles, should help to simplify the situation, especially when it is imbedded in the regulation and linked to control procedures. It would allow a balance between collective interests and the protection of individuals, taking into account of the international highly competitive scientific and economical constraints. The major issue is to preserve and to perpetuate the existing and future collections because of their precious value as an important tool for biomedical knowledge. The efficiency of a regulation depends on its legibility and accessibility, two requirements that seem to determine the acceptance of the regulatory tool and its application allowing subsequently to reach fairness in proceedings.

Ethics, Medical↗
PubMed2003

Segregation analysis of prostate cancer in France: evidence for autosomal dominant inheritance and residual brother-brother dependence.

Four segregation analyses concerning prostate cancer (CaP), three conducted in the United States and one in Northern Europe, have shown evidence for a dominant major gene but with different parameter estimates. A recent segregation analysis of Australian pedigrees has found a better fit of a two-locus model than single-locus models. This model included a dominantly inherited increased risk that was greater at younger ages and a recessively inherited or X-linked increased risk that was greater at older ages. Recent linkage analyses have led to the detection of at least 8 CaP predisposing genes, suggesting a complex inheritance and genetic heterogeneity. To assess the nature of familial aggregation of prostate cancer in France, segregation analysis was conducted in 691 families ascertained through 691 CaP patients, recruited from three French hospitals and unselected with respect to age at diagnosis, clinical stage or family history. This mode of family inclusion, without any particular selection of the probands, is unique, as probands from all previous analyses were selected according to various criteria. Segregation analysis was carried out using the logistic hazard regressive model, as incorporated in the REGRESS program, which can accommodate a major gene effect, residual familial dependences of any origin (genetic and/or environmental), and covariates, while including survival analysis concepts. Segregation analysis showed evidence for the segregation of an autosomal dominant gene (allele frequency of 0.03%) with an additional brother-brother dependence. The estimated cumulative risks of prostate cancer by age 85 years, among subjects with the at-risk genotype, were 86% in the fathers' generation and 99% in the probands' generation. This study supports the model of Mendelian transmission of a rare autosomal dominant gene with high penetrance, and demonstrates that additional genetic and/or common sibling environmental factors are involved to account for the familial clustering of CaP.

Age of Onset↗
PubMed2002

General review of maximal aerobic velocity measurement at laboratory. Proposition of a new simplified protocol for maximal aerobic velocity assessment.

The maximal aerobic velocity concept developed since eighties is considered as either the minimal velocity which elicits the maximal aerobic consumption or as the "velocity associated to maximal oxygen consumption". Different methods for measuring maximal aerobic velocity on treadmill in laboratory conditions have been elaborated, but all these specific protocols measure V(amax) either during a maximal oxygen consumption test or with an association of such a test. An inaccurate method presents a certain number of problems in the subsequent use of the results, for example in the elaboration of training programs, in the study of repeatability or in the determination of individual limit time. This study analyzes 14 different methods to understand their interests and limits in view to propose a general methodology for measuring V(amax). In brief, the test should be progressive and maximal without any rest period and of 17 to 20 min total duration. It should begin with a five min warm-up at 60-70% of the maximal aerobic power of the subjects. The beginning of the trial should be fixed so that four or five steps have to be run. The duration of the steps should be three min with a 1% slope and an increasing speed of 1.5 km x h(-1) until complete exhaustion. The last steps could be reduced at two min for a 1 km x h(-1) increment. The maximal aerobic velocity is adjusted in relation to duration of the last step.

Ergometry↗
PubMed2001

Evaluation of androgen, estrogen (ER alpha and ER beta), and progesterone receptor expression in human prostate cancer by real-time quantitative reverse transcription-polymerase chain reaction assays.

Steroid hormones can have profound effects on prostate tumor development making it important to define steroid receptor expression in prostate tissues. For this purpose, androgen receptor (AR) and estrogen receptor (ER alpha and ER beta) expression was quantified in 12 clinically localized and 11 hormone-refractory sporadic prostate tumors, using real-time quantitative reverse transcription-PCR assays. To gain more insight into hormone-responsiveness, estrogen-regulated progesterone receptor (PGR) and androgen-regulated prostatic acid phosphatase (PAP) mRNA levels were also quantified. There is a decrease in expression of ER beta in both clinically localized and hormone-refractory tumors relative to normal prostate tissues. Moreover, hormone-refractory tumors display a decreased expression of ER alpha and an increased expression of AR. There is a positive association between ER alpha, ER beta, and PGR expression (P < 0.0001) and a negative association between AR and the androgen-regulated gene PAP expression in hormone-refractory tumors. Taken together, these data indicate that, although increased expression of the AR gene might play a key role in endocrine treatment failure, it cannot be considered as the sole actor of this unresolved dilemma, and abnormalities in ER alpha and/or ER beta expression may also modulate the growth response of prostate cancer to hormone withdrawal. Our results also suggest that ER alpha and ER beta expression status could be used to identify advanced prostate tumor patients who may respond to antiestrogen therapy.

Acid Phosphatase↗
PubMed2001

In vivo model mimicking natural history of dog prostate cancer using DPC-1, a new canine prostate carcinoma cell line.

BACKGROUND: Dog prostate cancer is usually considered to be highly relevant to human prostate cancer. We report the isolation of a new canine prostate cancer epithelial cell line designated DPC-1. METHODS: Primary cultures were established from a canine poorly differentiated prostatic adenocarcinoma. Population doubling time was determined by counting nuclei after cell lysis. Tumorigenicity was assessed in nude mice and in one adult immunodeficient dog. Immunoscintigraphy was performed in both models using a monoclonal antibody (mAb) raised against the [44-62] sequence of human PSMA. RESULTS: DPC-1 cells have a rapid growth in vitro (doubling time, 27 hr) which is not stimulated by androgens. In addition, DPC-1 displays immunoreactivity to human PSA and PSMA. DPC-1 was found to be highly tumorigenic not only in nude mice but also for the first time after orthotopic seeding in an immunodeficient dog. This allograft mimicked, in a compressed form, the aggressive biological behavior of spontaneous dog prostate adenocarcinoma. Immunoscintigraphy using a (131)Iodine-labeled PSMA mAb clearly visualized induced tumors in nude mice and in the dog allograft. CONCLUSIONS: This study suggests that DPC-1 may constitute a powerful model for assessing new diagnostic and/or therapeutic tools in the management of prostate cancer.

Adenocarcinoma↗
PubMed2001

Establishment and characterisation of ovine blood monocyte-derived cell lines.

Studies of the important functions in host defense assured by macrophages, both as functional elements and as potential targets for intracellular pathogens, are often inhibited by the lack of a source of large numbers of uniform, well-characterised cells. To address this lack for ovine studies, we have established cell lines from spontaneously-proliferating adherent mononuclear cells from sheep blood. Eight such lines which have been continuously cultured for over 400 passages have phagocytic activities and cytochemical characteristics indicating that they retain the nature of mononuclear phagocytes. They display typical functional membrane proteins such as CD14, Fc receptors and MHC class II. Such cells can facilitate in vitro studies of pathogen-monocyte interactions and can furnish copious amounts of cells for transfer experiments.

Acid Phosphatase↗
PubMed2001

Noninvasive detection of genetic instability in cells from prostatic secretion as a marker of prostate cancer.

We present a clinical and molecular study of a series of specific loss of heterozygosity (LOH) indicators which, together with PSA, increase the predictability of cancer in early prostate cancer patients. Considering a positive biopsy as the standard reference, the testing parameters for LOH testing are better than the PSA F/T ratio (<25%), suggesting that this noninvasive approach to detecting early prostate cancer could be very useful as a new tool to optimize the indications for iterative prostate biopsies.

Journal Article↗
PubMed2001

PCAP is the major known prostate cancer predisposing locus in families from south and west Europe.

To date four prostate cancer predisposing loci have been mapped: HPC1 (Hereditary Prostate Cancer 1) on 1q24-25, PCaP (Predisposing for Cancer Prostate) on 1q42.2-43, CAPB (Cancer Prostate and Brain) on 1p36, and HPCX on Xq27-28. We examined evidence for linkage to those loci in 64 families from south and west Europe. Genotyping of three (six for PCaP) markers encompassing the candidate regions were performed on 221 individuals including 159 affected patients. The resulting data were analysed using both parametric and non parametric linkage methods. No significant evidence of linkage to HPC1, CAPB, or HPCX was found either in the whole population or when pedigrees were stratified according to criteria specific to each locus. By contrast, results in favour of linkage to PCaP locus were observed with maximum multipoint NPL and HLOD scores of 2.8 (P = 0.0026) and 2.65 respectively. Homogeneity analysis performed with multipoint LOD scores gave an estimated proportion of families with linkage to this locus up to 50%. Particularly, families with an earlier age at diagnosis (< or = 65-years-old) contributed significantly to the evidence of linkage with a maximum multipoint NPL score of 2.03 (P = 0.024). Those results suggest that PCaP is the most frequent known locus predisposing to hereditary prostate cancer cases from families from south and west Europe.

Aged↗
PubMed2000

Early-onset hereditary prostate cancer is not associated with specific clinical and biological features.

BACKGROUND: Familial prostate cancer (CaP) accounts for 15-20% of all CaP, and hereditary CaP for 5-10% of patients. Few data are available concerning their clinical and biological features. METHODS: We compared diagnostic modalities, age, clinical stage, PSA, and tumor grade at diagnosis in CaP patients according to familial CaP profile: hereditary (HR) (> or =3 CaP), familial nonhereditary (FNH) (= 2 CaP), and sporadic CaP. Only cases diagnosed after January 1, 1987 (PSA-available period) were included. We considered as informative sporadic (IS) cases those probands with 2+ nonaffected brothers at least 50 years old. Finally, 267 CaP (230 probands and 37 affected brothers) were studied. RESULTS: In multivariate analysis, the only specific parameter significantly associated with HR and FNH CaP was early age at diagnosis; mean ages were 65.3 years (HR), 67 years (FNH), and 70.9 years (IS) (P < 0. 0001). No significant difference was observed concerning clinical stage, PSA, and tumor grade. In addition, diagnostic modalities were similar in the three groups. CONCLUSIONS: Our data confirm the occurrence of early-onset CaP in hereditary families. Although the clinical and biological presentation of HR CaP remains controversial, the lack of specific features observed in our study leads us to conclude that there is no difference in the aggressiveness of the disease in hereditary compared to sporadic CaP.

Aged↗
PubMed2000

Early onset and familial predisposition to prostate cancer significantly enhance the probability for breast cancer in first degree relatives.

Genetic predisposition accounts for >/=10% of all cancer of the prostate (CaP) and is therefore considered a major risk factor, together with age and ethnic origin. Several epidemiological studies have suggested that familial clustering of CaP may be associated with an increased frequency of breast and other cancers among relatives. In order to correlate the incidence of CaP with prevalence of breast and other cancers, we have performed uni- and multi-variate analyses on 691 complete pedigrees including probands, who were consecutive patients with confirmed CaP treated in three French urological departments. We have shown a significantly higher risk (RR = 2.3, p = 0.01) to develop breast cancer in families with multiple than in those with a single CaP. Risk of observing other types of cancer within these families was not significant. We then calculated the breast cancer risk in early onset prostate cancer families, and observed a relative risk that is even more significant (RR = 5.5, p = 0.002). Furthermore, the risk was >30 times that a proband's mother have breast cancer if CaP occurred below 55 years of age, rather than after 75 years (p = 0.003). This study has therefore shown for the first time, the relatively high penetrance for breast cancer in relatives of early onset CaP patients.

Adult↗
PubMed2000

Gene transfer to urethral strictures in rabbits: a preliminary report.

OBJECTIVE: To assess the rationale for virus-mediated gene transfer into the urethra in vivo and in vitro, using a rabbit model, as this is an attractive approach to prevent recurrence after the endoscopic management of urethral strictures. MATERIALS AND METHODS: Primary cultures of rabbit urethral stromal cells were infected with adenoviral and retroviral solutions carrying a nucleus-targeted beta-galactosidase (beta-Gal) reporter gene (respectively 109 and 107 plaque-forming units/mL). In addition, to mimic the human clinical situation, a model was developed of thermally induced stricture in rabbit urethra which produced fibrotic stenosis within 15 days. Using a prototype channelled balloon catheter, these strictures were endoscopically dilated and then instilled with the beta-Gal adenoviral or retroviral constructs. RESULTS: The application of recombinant adenovirus and retrovirus harbouring a nucleus-targeted beta-Gal reporter gene to cultured rabbit urethral stromal cells resulted in a high transduction efficiency of up to 90% and 96%, respectively. Five days after infection, histochemical and immunohistochemical staining of the strictured urethrae showed a 3% rate of transfection targeted to stromal cells within the fibrosis, confirmed by polymerase chain reaction (PCR) analysis. Adjacent and distal spread of the virus was excluded by histochemistry, immunohistochemistry and PCR. CONCLUSION: These results represent the first report of endoscopic adenovirus and retrovirus-mediated gene transfer to the urethra. Although at a low rate, transduction reached stromal cells transmurally within the induced strictures and was site-specific.

Adenoviridae↗
PubMed2000

Androgen receptor localisation and turnover in human prostate epithelium treated with the antiandrogen, casodex.

In vitro models of normal and malignant human prostate are currently limited to a few well established cell lines that, with a single exception (LNCaP), fail to express the androgen receptor (AR) - a common characteristic of prostatic epithelium grown in culture. To investigate the molecular mechanism of action of the non-steroidal antiandrogen Casodex (bicalutamide) against wild-type AR, we have established a transient AR expression model in non-tumorigenic prostate cells of both epithelial and mesenchymal origin. In this model, both dihydrotestosterone and Casodex can effectively transport the AR protein into the nucleus of prostate cells. Whereas the natural ligand, dihydrotestosterone, stabilises the receptor, the AR is rapidly degraded at a nuclear location when the transfected cells are treated with Casodex. In contrast, whereas the mutant AR in the LNCaP line is also degraded on Casodex treatment over the same time period, its intracellular targeting is defective.

Androgen Antagonists↗
PubMed2000

Changes in cortisol and testosterone levels and T/C ratio during an endurance competition and recovery.

BACKGROUND: To describe the evolution of cortisol and testosterone levels and testosterone/cortisol (T/C) ratio in long-distance runners during a relay competition and during the three days following the competition. METHODS: Two teams of four relayers (one male, one female) took part into this six-hour relay race. Hormonal control during the race was made possible thanks to saliva sampling during rest periods at each relay. The runners were subelite runners, (VO2max = 67.0 ml x min(-1) x kg(-1) in males and 56.8 ml x min(-1) x kg(-1) in females). RESULTS: During the race, cortisol levels reached approximately 1.5-fold basal levels. These levels remained high till late evening, (higher than morning values, when normal resting levels are 4 to 6-folds lower). Surprisingly, wakening levels during the following days were lower than resting levels. Testosterone did not vary in females; then, male values only are reported. During the race they decreased gradually and remained low till night. During the following three days, testosterone levels were higher than resting day levels. The T/C ratio amplifies these variations: low during the race till retiring, (currently associated with a catabolic tendency) and reversely high during the following three days (associated with a high anabolic tendency). CONCLUSIONS: As expected, a catabolic tendency occurs during a long distance run (increase in cortisol level followed by a drop in testosterone level). More surprising is the high anabolic tendency noted during the recovery period (low cortisol and high testosterone levels).

Adult↗
PubMed1999

FGF7/KGF triggers cell transformation and invasion on immortalised human prostatic epithelial PNT1A cells.

Fibroblast growth factor 7 (FGF7/KGF) is synthesized exclusively by fibroblasts in normal tissues; it acts as a potent mitogen on epithelial cells, through interaction with the FGF7-specific receptor FGFR2/IIIb. To examine the importance of this growth factor both to prostate physiology and to prostate-cancer progression, we have tested the exogenous effect of FGF7. Thus, by mimicking the paracrine pathway (on proliferation, growth in soft agar and invasion) on the human prostatic epithelial cell line PNT1A positively checked for FGFR2/IIIb expression, FGF7 significantly enhanced cell proliferation at an optimal concentration of 7.5 x 10(-11) M, but no significant invasion or growth in soft agar were observed. To confirm FGF7 properties on human prostatic epithelial cells, we constitutively expressed FGF7 by transfecting PNT1A cells with FGF7-cDNA. The FGF7-transfected clones, PNT1A/ FGF7-T5 and PNT1A/FGF7-T6, were stable and expressed FGF7. Analysis of the FGF7-autocrine loop on the non-tumorigenic epithelial cells PNT1A showed acquired invasive potential in in vitro extracellular-matrix migration assays, specifically inhibited by an FGF7-neutralizing antibody, and over-expressed factors implicated in the migration process: the metalloproteinase MMP-1 and the plasminogen activator uPA. Taken together, these results demonstrate a role for FGF7 in triggering invasion of human prostatic epithelial cells. Furthermore, these FGF7-transfected clones exhibited functional and physiological differences from the original PNT1A cell line: anchorage-independent growth, growth in serum-free media and increased proliferation. These data confirm the oncogenic function of FGF7 in prostate progression potentially acting through paracrine and/or autocrine regulatory pathways.

Cell Division↗
PubMed1999

Upregulation of endothelin 1 and its precursor by IL-1beta, TNF-alpha, and TGF-beta in the PC3 human prostate cancer cell line.

Increasing evidence indicates that endothelin 1 (ET-1) is implicated in prostate tumour progression. However, data on ET-1 regulation in human prostate and prostate cancer cell lines are lacking. In this study, regulation of ET-1 and its precursor big ET-1, using PC3 cells, a human bone metastatic prostatic carcinoma cell line, was addressed. ET-1 and big ET-1 assays demonstrated greater secretion of both peptides in the presence of 10% fetal calf serum (FCS) as compared with 0.5% FCS. Incubation of PC3 cells in the absence and presence of various cytokines and growth factors known to be implicated in prostate stroma-epithelium interactions, revealed that IL-6, FGF7/KGF and FGF2/bFGF had no effect on ET-1 and big ET-1 secretion, whereas interleukin 1beta (IL-1beta), tumour necrosis factor alpha (TNF-alpha) and transforming growth factor beta (TGF-beta) stimulated their secretion in a concentration-dependent manner. Binding experiments indicated the presence of specific ET-1 receptors in PC3 cells: Kdapp = 1.1 x 0.2 x 10(-10)M, Bmax = 2660 +/- 390 sites/cell. Data analysis demonstrated the presence of only the ETA receptor subtype in PC3 cells. In conclusion, our results indicate that the implication of ET-1 in prostate cancer is likely to be mediated via paracrine/autocrine control of cell factors.

Cytokines↗